The ability to kill cells provides a powerful therapeutic approach to treatment of disease or infection. Bacteria and fungi are becoming resistant to many of the currently available antimicrobial or antimycotic therapeutic compounds. Cancer cells frequently acquire mutations that enhance resistance to standard treatments. Principal among these mechanisms of drug resistance is abnormal expression of members of the B cell lymphoma-2 (Bcl-2) family (Oltersdorf et al., 2005). The Bcl-2 family consists of more than twenty anti- and pro-apoptotic members that modulate the balance between life and death. Tumors expressing high levels of anti-apoptotic proteins, such as Bcl-2, Mcl-1 or Bcl-xl, can be resistant to the effects of chemotherapeutics (Oltersdorf et al., 2005). This is accomplished, in part, by inhibition of the pro-apoptotic Bcl-2 family members, such as Bax, first identified as a protein that interacts with Bcl-2 (Oltvai et al., 1993). The association of Bax with mitochondria is linked to the release of cytochrome c and other death-mediators from mitochondrial reserves (Eskes et al., 1998).
Bax is a 21 kD protein of 192 amino acids, comprised of nine alpha helices (Suzuki et al., 2000). Under non-apoptotic conditions, Bax predominantly resides in the cytosol, with a small percentage of the protein localized to the mitochondria (Boohaker et al., 2011; Kaufmann et al., 2003; Putcha et al., 1999).
Despite advances in understanding the physiology and pathophysiology of cancer and/or aberrant cell growth, there is still a scarcity of compounds that are efficacious and safe in the treatment of cancer and/or aberrant cell growth. Therapeutics that are effective against bacteria and fungi are needed as these microorganisms grow more resistant to current therapies. These needs and other needs are satisfied by the present invention.